Luodan Yu

Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r1 = 9.43 mM-1 s-2) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.

Two-Dimensional Ultrathin MXene Ceramic Nanosheets for Photothermal Conversion

Ceramic biomaterials have been investigated for several decades, but their potential biomedical applications in cancer therapy have been paid much less attentions, mainly due to their lack of related material functionality for combating the cancer. In this work, we report, for the first time, that MAX ceramic biomaterials exhibit the unique functionality for the photothermal ablation of cancer upon being exfoliated into ultrathin nanosheets within atomic thickness (MXene). As a paradigm, biocompatible Ti3C2 nanosheets (MXenes) were successfully synthesized based on a two-step exfoliation strategy of MAX phase Ti3AlC2 by the combined HF etching and TPAOH intercalation. Especially, the high photothermal-conversion efficiency and in vitro/in vivo photothermal ablation of tumor of Ti3C2 nanosheets (MXenes) were revealed and demonstrated, not only in the intravenous administration of soybean phospholipid modified Ti3C2 nanosheets but also in the localized intratumoral implantation of a phase-changeable PLGA/Ti3C2 organic-inorganic hybrid. This work promises the great potential of Ti3C2 nanosheets (MXenes) as a novel ceramic photothermal agent used for cancer therapy and may arouse much interest in exploring MXene-based ceramic biomaterials to benefit the biomedical applications.

Site-specific sonocatalytic tumor suppression by chemically engineered single-crystalline mesoporous titanium dioxide sonosensitizers

The biomedical applications of TiO2-based nanosystems develop very slowly among diverse inorganic bio-nanosystems (e.g., Fe3O4, SiO2, MnO, Au, etc.) due to the lack of adequate synthetic strategies to fabricate TiO2 nanoparticles with desirable nanostructures and their specific light responses in the ultraviolet range with potential phototoxicity and low tissue-penetrating capability. In this work, we report on the rational design and fabrication of colloidal single-crystalline and mesoporous anatase TiO2 nanoparticles (MTNs) with high dispersity, well-defined mesoporosity, uniform morphology and nanosized single-crystalline structure, employing a facile yet versatile bottom-up chemical strategy, i.e., pre-hydrolysis of titanium precursors combined with subsequent solvothermal treatment (PH-ST) simply using water as the additive. Highly biocompatible PEGylated MTNs have exerted their unique function as efficient sonosensitizers for sonodynamic therapy (SDT) of cancer, as systematically demonstrated both in vitro and in vivo. The production of reactive oxygen species (ROS) by MTN-sonosensitized SDT has been demonstrated to be the mechanism for efficient tumor SDT. The in vivo biocompatibility assay revealed that either a single dose at 150 mg kg-1 or repeated doses at as high as a total of 400 mg kg-1 exhibited no obvious in vivo toxicity. The ultrasound irradiation of MTNs in SDT is expected to break the depth shadow of light responsiveness of TiO2-based nanosystems in the ultraviolet range, and the presence of well-defined mesoporous nanostructures of MTNs shows great potential for the delivery of therapeutic agents for combined cancer therapy.

Ultrasmall mesoporous organosilica nanoparticles: Morphology modulations and redox-responsive biodegradability for tumor-specific drug delivery

Beyond mesoporous silica nanoparticles (MSNs), mesoporous organosilica nanoparticles (MONs) have been becoming an even more attractive alternative to the traditional organic or inorganic nanomaterials in biomedical applications, especially for drug delivery, due to its high surface area, stable physicochemical properties, low toxicity, high biocompatibility, and particularly the devisable features decided by the incorporated organic fragments. However, it is still challenging to fabricate uniform ultrasmall MONs with tunable composition, morphology and fine biodegradability. Herein, we report, on the large-scale fabrication of monodispersed and molecularly organic-inorganic hybrid MONs with framework-incorporated physiologically active thioether bonds, controllable nanostructure, composition and morphology, which provides the material foundation for exploring the versatile biomedical applications of organosilica nanosystems. The hybrid MONs of less than 50 nm in particle size exhibit the unique reduction-responsive biodegradation behavior, and the biodegradation rate is significantly higher than that of traditional mesoporous silica nanoparticles with pure inorganic SiOSi framework. The reductive microenvironment-triggered biodegradation of MONs induces the concurrent reduction-responsive anticancer drug releasing from MONs, enabling tumor-specific drug delivery. Importantly, these biocompatible and biodegradable MONs exhibit significantly improved drug-delivery efficiency and enhanced tumor-suppressing effect for combating cancer. Based on the facile and large-scale fabrication of MONs with controllable key structure/composition/morphology parameters, unique tumor microenvironment-responsive biodegradation behavior and high performance for drug delivery, the MONs therefore show more promising potentials for clinical translation as compared to traditional MSNs.

A Compact High-Accuracy Rail-to-Rail CMOS Operational Amplifier

A compact high-accuracy rail-to-rail CMOS operational amplifier (Op-Amp) is presented using strong inversion techniques to achieve power consumption of 90µW under 1.8V supply voltage. Two complementary differential pair techniques and one-versus-three current mirror compensation techniques are adopted to realize wide input dynamic range, while the output stage provides rail-to-rail output drive through the use of resistor-compensation circuits (RCC) and self-regular circuits (SRC). Simulation results demonstrated that the active area is only 0.001mm2 and the transconductance variation can be restricted to ±±5% hence the accurate of common-mode rang (99.9%) was improved as well as the total harmonic distortion.

Generic synthesis and versatile applications of molecularly organic–inorganic hybrid mesoporous organosilica nanoparticles with asymmetric Janus topologies and structures

Precise control over the morphology, nanostructure, composition, and particle size of molecularly organic–inorganic hybrid mesoporous organosilica nanoparticles (MONs) still remains a major challenge, which severely restricts their broad applications. In this work, an efficient bridged organic group-determined growth strategy has been proposed for the facile synthesis of highly dispersed and uniform MONs with multifarious Janus morphologies, nanostructures, organic–inorganic hybrid compositions, and particle sizes, which can be easily controlled simply by varying the bridged organic groups and the concentration of bis-silylated organosilica precursors used in the synthesis. In addition, the formation mechanism of Janus MONs determined by the bridged organic group has been discussed. Based on the specific structures, compositions, and asymmetric morphologies, all the synthesized Janus MONs with hollow structures (JHMONs) demonstrate excellent performances in nanomedicine as desirable drug carriers with high drug-loading efficiencies/capacities, pH-responsive drug releasing, and enhanced therapeutic efficiencies, as attractive contrast-enhanced contrast agents for ultrasound imaging, and as excellent bilirubin adsorbents with noticeably high adsorption capacities and high blood compatibilities. The developed versatile synthetic strategy and the obtained JHMONs are extremely important in the development and applications of MONs, particularly in the areas of nanoscience and nanotechnology.

Magnesium-Engineered Silica Framework for pH-Accelerated Biodegradation and DNAzyme-Triggered Chemotherapy

Inorganic nanocarriers have shown their high performance in disease theranostics in preclinical animal models and further great prospects for clinical translation. However, their dissatisfactory biodegradability and pre-drug leakage with nonspecificity to lesion sites significantly hinders the possible clinical translation. To solve these two critical issues, a framework-engineering strategy is introduced to simultaneously achieve enhanced biodegradability and controllable drug releasing, based on the mostly explored mesoporous silica-based nanosystems. The framework of mesoporous silica is engineered by direct Mg doping via a generic dissolution and regrowth approach, and it can transform into the easy biodegradation of magnesium silicate nanocarriers with simultaneous on-demand drug release. Such magnesium silicate nanocarriers can respond to the mild acidic environment of tumor tissue, causing the fast breaking up and biodegradation of the silica framework. More interesting, the released Mg2+ can further activate Mg2+ -dependent DNAzyme on the surface of hollow mesoporous magnesium silicate nanoparticles (HMMSNs) to cleave the RNA-based gatekeeper, which further accelerates the release of loaded anticancer drugs. Therefore, enhanced anticancer efficiency of chemotherapeutic drugs assisted by the biodegradable intelligent HMMSNs is achieved. The high biocompatibility of nanocarriers and biodegradation products is demonstrated and can be easily excreted via feces and urine guaranteeing their further clinical translation.

Theranostic nanomedicine by surface nanopore engineering

Theranostic nanomedicine that integrates diagnostic and therapeutic agents into one nanosystem has gained considerable momentum in the field of cancer treatment. Among diverse strategies for achieving theranostic capabilities, surface-nanopore engineering based on mesoporous silica coating has attracted great interest because of their negligible cytotoxicity and chemically active surface that can be easily modified to introduce various functional groups (e.g., −COOH, −NH2, −SH, etc.) via silanization, which can satisfy various requirements of conjugating biological molecules or functional nanoparticles. In addition, the nanopore-engineered biomaterials possess large surface area and high pore volume, ensuring desirable loading of therapeutic guest molecules. In this review, we comprehensively summarize the synthetic procedure/paradigm of nanopore engineering and further broad theranostic applications. Such nanopore-engineering strategy endows the biocompatible nanocomposites (e.g., Au, Ag, graphene, upconversion nanoparticles, Fe3O4, MXene, etc.) with versatile functional moieties, which enables the development of multifunctional nanoplatforms for multimodal diagnostic bio-imaging, photothermal therapy, photodynamic therapy, targeted drug delivery, synergetic therapy and imaging-guided therapies. Therefore, mesoporous silica-based surface-nanopore engineering integrates intriguing unique features for broadening the biomedical applications of the single mono-functional nanosystem, facilitating the development and further clinical translation of theranostic nanomedicine.

Photonic Cancer Nanomedicine at Near Infrared-II Biowindow Enabled by Biocompatible Titanium Nitride Nanoplatforms

Light-activated photoacoustic imaging (PAI) and photothermal therapy (PTT) using the second near-infrared biowindow (NIR-II, 1000-1350 nm) hold great promise for efficient tumor detection and diagnostic imaging-guided photonic nanomedicine. In this work, we report on the construction of titanium nitride (TiN) nanoparticles, with a high photothermal-conversion efficiency and desirable biocompatibility, as an alternative theranostic agent for NIR-II laser-excited photoacoustic (PA) imaging-guided photothermal tumor hyperthermia. Working within the NIR-II biowindow provides a larger maximum permissible exposure (MPE) and desirable penetration depth of the light, which then allows detection of the tumor to the full extent using PA imaging and complete tumor ablation using photothermal ablation, especially in deeper regions. After further surface polyvinyl-pyrrolidone (PVP) modification, the TiN-PVP photothermal nanoagents exhibited a high photothermal conversion efficiency of 22.8% in the NIR-II biowindow, and we further verified their high penetration depth using the NIR-II biowindow and their corresponding therapeutic effect on the viability of tumor cells in vitro. Furthermore, these TiN-PVP nanoparticles were developed as a contrast agent for NIR-II-activated PA imaging both in vitro and in vivo for the first time and realized efficient photothermal ablation of the tumor in vivo within both the NIR-I and NIR-II biowindows. This work not only provides a paradigm for TiN-PVP photothermal nanoagents working in the NIR-II biowindow both in vitro and in vivo, but also proves the feasibility of PAI and PTT cancer theranostics using NIR-II laser excitation.

Multifunctional Mesoporous Silica Nanoprobes: Material Chemistry-Based Fabrication and Bio-Imaging Functionality

Nanoparticles‐based bioimaging probes are attracting broad attention for various biomedical applications. As one of the mostly explored nanoplatforms, mesoporous silica nanoparticles (MSNs) show high clinical‐translation potential for diagnostic probing/imaging. Based on their tunable morphology, abundant surface chemistry, and well‐defined mesostructure, MSNs are regarded as the desirable platforms for constructing diverse nanoprobes via incorporation of a variety of functional moieties or components. In this review, the authors summarize and discuss recent progress in the rational design and fabrication of multifunctional mesoporous silica‐based composite nanoprobes for versatile bioimaging applications. Four kinds of methodologies for the fabrication of these mesoporous silica‐based nanoprobes are discussed, including encapsulating functional nanoparticles within a mesoporous silica shell, assembling functional nanoparticles on the surface of MSNs, dispersing nanoparticles into the nanometer‐scale mesopores of MSNs, and doping functional moieties into the framework of MSNs. The applications of mesoporous silica nanoprobes in magnetic resonance imaging, ultrasound imaging, computed tomography imaging, fluorescence imaging, positron emission computed tomography, photoacoustic (PA) imaging, and even multimodality imaging are discussed in detail. The biosafety of MSN‐based composite nanoplatforms as bioimaging nanoprobes is also highlighted, accompanied by a deep discussion on facing the challenges and future developments for guaranteeing their further potential clinical translation.